The overall goal of the General Clinical Research Center (GCRC) at Dallas is to provide an optimal environment for patient-oriented investigation which leads to an improved understanding of the disease process, allows better methods of diagnosis and treatment, foster interdisciplinary collaboration, and offers training in clinical investigation. Major activities of the GCRC include; to study efficacy and safety of adding a bisphosphonate to sustained-release sodium fluoride (Neosten) and to evaluate a new formulation of sustained-release sodium fluoride combined with calcium citrate (Caflor) for postmenopausal osteoporosis; to utilize newer techniques for assessment of bone quality in osteoporosis such as nuclear magnetic resonance (NMR) microscopy, critical angle reflection ultrasound and strut analysis; determination of the pathophysiology, particularly relate to insulin resistance in gouty diathesis (renal stone formation associated with gout), its molecular genetic basis and the effects of improving insulin sensitivity in reversing the biochemical defects; elucidation of the genetic basis of low levels of high density lipoprotein (HDL) as related to the polymorphisms in hepatic lipase gene; characterization of phenotype and metabolic abnormalities, and elucidation of genetic defects in patients with congenital generalized and familial partial lipodystrophies; to study efficacy and safety of adding methotrexate therapy to ursodeoxycholic acid for therapy of primary billiary cirrhosis in a randomized, blinded, placebo-controlled trial; comparison of innovative and conventional treatments for management of or develop surrogate biologic markers predicting predisposition to specific skin diseases and response to therapy; to study neural mechanisms of obesity-related hypertension in African-Americans utilizing microelectrode recordings of postganglionic sympathetic nerve activity; and development of new and reliable techniques to assess renal functions and to perform safety and dose-ranging studies of alpha- melanocyte stimulating hormone (MSH) for subsequent clinical trials of alpha-MSH to treat or prevent acute renal failure.